Login Register Cart 0
Generic placeholder image

Current Diabetes Reviews

Editor-in-Chief

ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Perspective

Redefining Cardiovascular (CV) Death as a Primary Endpoint Component in Cardiovascular Outcome Trials

Author(s): Samit Ghosal* and Binayak Sinha

Volume 16, Issue 9, 2020

Page: [917 - 921] Pages: 5

DOI: 10.2174/1573399816666200206113549

Price: $65

Abstract

Sodium-Glucose cotransporter-2 inhibitors (SGLT-2i) and Glucagon-like peptide 1 receptor agonists (GLP1-RA) have revolutionised the approach for modern management of type 2 diabetes in view of their outcome altering abilities. An objective component of the primary endpoints used in the Cardiovascular Outcome Trials (CVOT) is cardiovascular (CV) death. However, the reason behind the decrease in CV deaths (compared to the placebo arm) appear to arise from divergent underlying processes. A recent meta-analysis of SGLT-2i and GLP1-RA indicated that the reduction in CV death associated with the former is predominantly due to its impact on heart failure (HF), while the association with the latter is due to its effect on atherosclerotic cardiovascular disease (ASCVD). A Pearson’s product- moment correlation coefficient (r) analysis was performed on SGLT-2i exposed to CVOTs, exploring the strength of the association between CV death and hospitalisation for HF (hHF) and myocardial infarction (MI). The strength of association was strongest with hHF and negative with MI. In view of these findings, it has been proposed that future CVOTs should use a more objective definition of CVD, defining well in advance the anticipated impact on CVD (either as a consequence of the reduction in HF or ASCVD).

Keywords: CVOT, MACE, MI, hHF, SGLT-2i, CV death, type 2 diabetes, correlation coefficient.

[1]
Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007; 356(24): 2457-71.
[http://dx.doi.org/10.1056/NEJMoa072761] [PMID: 17517853]
[2]
U.S. Food and Drug. 2008.https://www.fda.gov/regulatory-information/search-fda-guidance-documents/diabetes-mellitus-evaluating-cardiovascular-risk-new-antidiabetic-therapies-treat-type-2-diabetes
[3]
Smith RJ, Goldfine AB, Hiatt WR. Evaluating the cardiovascular safety of new medications for type 2 diabetes: time to reassess? Diabetes Care 2016; 39(5): 738-42.
[http://dx.doi.org/10.2337/dc15-2237] [PMID: 27208377]
[4]
Ghosal S, Sinha B, Bhattacharjee K. Cardio Vascular Outcomes Trials (CVOTs) with anti-hyperglycemic agents: demystifying statistical complexities. J Diabetes Metab Disord Control 2017; 4: 104-8.
[http://dx.doi.org/10.15406/jdmdc.2017.04.00116]
[5]
Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015; 373(3): 232-42.
[http://dx.doi.org/10.1056/NEJMoa1501352] [PMID: 26052984]
[6]
Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013; 369(14): 1317-26.
[http://dx.doi.org/10.1056/NEJMoa1307684] [PMID: 23992601]
[7]
White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013; 369(14): 1327-35.
[http://dx.doi.org/10.1056/NEJMoa1305889] [PMID: 23992602]
[8]
Rosenstock J, Perkovic V, Johansen OE, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the carmelina randomized clinical trial. JAMA 2019; 321(1): 69-79.
[http://dx.doi.org/10.1001/jama.2018.18269] [PMID: 30418475]
[9]
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373(22): 2117-28.
[http://dx.doi.org/10.1056/NEJMoa1504720] [PMID: 26378978]
[10]
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377(7): 644-57.
[http://dx.doi.org/10.1056/NEJMoa1611925] [PMID: 28605608]
[11]
Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019; 380(4): 347-57.
[http://dx.doi.org/10.1056/NEJMoa1812389] [PMID: 30415602]
[12]
Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016; 375(4): 311-22.
[http://dx.doi.org/10.1056/NEJMoa1603827] [PMID: 27295427]
[13]
Sinha B, Ghosal S. Sodium-glucose cotransporter-2 inhibitors (sglt-2i) reduce hospitalization for heart failure only and have no effect on atherosclerotic cardiovascular events: a meta-analysis. Diabetes Ther 2019; 10(3): 891-9.
[http://dx.doi.org/10.1007/s13300-019-0597-3] [PMID: 30875065]
[14]
Mannucci E, Dicembrini I, Nreu B, Monami M. Glucagon‐like peptide‐1 receptor agonists and cardiovascular outcomes in patients with and without prior cardiovascular events: An updated meta‐analysis and subgroup analysis of randomized controlled trials. Diabetes Obes Metab 2019; 22(2): 203-11.
[http://dx.doi.org/10.1111/dom.13888] [PMID: 31595657]
[15]
Sinha B, Ghosal S. Meta-analyses of the effects of DPP-4 inhibitors, SGLT2 inhibitors and GLP1 receptor analogues on cardiovascular death, myocardial infarction, stroke and hospitalization for heart failure. Diabetes Res Clin Pract 2019; 150: 8-16.
[http://dx.doi.org/10.1016/j.diabres.2019.02.014] [PMID: 30794833]
[16]
Zelniker TA, Wiviott SD, Raz I, et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus. Circulation 2019; 139(17): 2022-31.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038868] [PMID: 30786725]
[17]
Packer M. Drugs that ameliorate epicardial adipose tissue inflammation may have discordant effects in heart failure with a preserved ejection fraction as compared with a reduced ejection fraction. J Card Fail 2019; 25(12): 986-1003.
[http://dx.doi.org/10.1016/j.cardfail.2019.09.002] [PMID: 31541742]
[18]
Mudaliar S, Alloju S, Henry RR. Can a shift in fuel energetics explain the beneficial cardiorenal outcomes in the EMPA-REG OUTCOME Study? A unifying hypothesis. Diabetes Care 2016; 39(7): 1115-22.
[http://dx.doi.org/10.2337/dc16-0542] [PMID: 27289124]
[19]
Lan NSR, Fegan PG, Yeap BB, Dwivedi G. The effects of sodium-glucose cotransporter 2 inhibitors on left ventricular function: current evidence and future directions. ESC Heart Fail 2019; 6(5): 927-35.
[http://dx.doi.org/10.1002/ehf2.12505] [PMID: 31400090]
[20]
Hee-Sook J. Anti-inflammatory effects of GLP-1-based therapies beyond glucose control. Mediators Inflamm 2016; 2016: 1-11.
[21]
Mukaka MM. Statistics corner: A guide to appropriate use of correlation coefficient in medical research. Malawi Med J 2012; 24(3): 69-71.
[PMID: 23638278]
[22]
Cefalu WT, Kaul S, Gerstein HC, et al. Cardiovascular outcomes trials in type 2 diabetes: where do we go from here? reflections from a diabetes care editors’ expert forum. Diabetes Care 2018; 41(1): 14-31.
[http://dx.doi.org/10.2337/dci17-0057] [PMID: 29263194]
[23]
Rajput R, Prakash A, Aggarwal R. Newer antidiabetic drugs in the pipeline. Int J Diab 2019; pp. 28-33.
[24]
McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019; 381(21): 1995-2008.
[http://dx.doi.org/10.1056/NEJMoa1911303] [PMID: 31535829]
[25]
Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet 2018; 392(10157): 1519-29.
[http://dx.doi.org/10.1016/S0140-6736(18)32261-X] [PMID: 30291013]

Rights & Permissions Print Cite
Article Metrics
58
© 2024 Bentham Science Publishers | Privacy Policy